Neurotoxins and neurodegenerative disorders.

There is a hypothesis that excitotoxic pathomechanisms underlie neuronal tissue degeneration in neurological disorders. It is proposed that target neurons are overexcited, the result being energy disturbance and pathobiochemical changes that culminate in nerve cell death. Domoic acid (structural analogue of kainic acid) and beta-N-oxalylamino-L-alanine (BOAA) are powerful excitotoxins. Diminished energy supplies may result either in excessive release of glutamate or an inability of the neuron to restore ionic balance after stimulation. Impairment of intracellular energy metabolism induced by cyanide, amino-oxyacetic acid (AOAA), 3-acetylpiridine, thiamine deficiency, azide, 3-nitropropionic acid, methyl-phenyltetrahydro-pyridinum ion (MPP+), carbon monoxide, methanol intoxication and manganese (Mn) is discussed. Furthermore, the endogenous substance kynurenine is metabolised to kynurenic acid (excitotoxin antagonist) and quinolinic acid (excitotoxin agonist) Probenecid (inhibitor of kynurenic acid excretion from the extracellular fluid) has an antiexcitatory effect.